Thyroid Pathology Review
What thyroid condition causes a persistent sore throat with a painful thyroid and fever?
Dequervain or giant cell thyroiditis, aka subacute granulomatous thyroiditis
more in women 10-40???
An elder whose CHF has just gotten worse may have what thyroid condition?
"apathetic" hypothyroidism
If someone just had a coxsackie virus infection and now is hyperthyroid, what do you suspect?
subacute granulomatous thyroiditis
What is the morphology of thyroid follicles in Grave's disease?
Follicles are scalloped in appearance, “all chewed up”
What is TSI most specific for?
Graves
What two diseases have both anti-thyroglobulin and anti-thyroperoxidase antibodies?
Hashimotos and Graves
What enzyme links iodine to tyrosine?
peroxidase
Which goiters are the largest, and can "plunge" behind the sternum?
thyrotoxic multinodular, aka Plummer dz, most mistaken for cancer
What kind of thyroiditis makes the gland wooden or rock-hard?
Reidel thyroiditis, rare condition in older women, may cause hypothyroidism or dyspnea
What percentage of solitary thyroid nodules are adenomas?
99%
What kind of thyroid carcinoma shows "Orphan Annie eye" nuclei?
papillary
also as psammomma bodies
What's the most common kind of thyroid carcinoma?
papillary carcinoma (75-80%)
What hormone do they have receptors for?
estrogen
What is the usual cell of origin for thyroid neoplasms?
follicular epithelium
What less common cancer arises from C cells in the follicular epithelium?
medullary carcinoma
What do C cells make?
calcitonin
VIP, serotonin, somatostatin, ACTH
(calcitonin used as tumor marker for medullary)
What's the second most common primary thyroid cancer?
follicular carcinoma (10-20% of thyroid CA)
10 year survival for larger tumors is 50%
most are cold, may be warm
Name three bone tropic hormones.
thryrocalcitonin
estrogen (esp E1 and E2)
progesterone
testosterone
DHEA
Name two bone resorptive hormones.
PTH, T3, T4, cortisol
How may raw cruciferous vegetables and African cassava (aka tapioca) affect the thyroid?
They are goitrogens, ie. they suppress the function of the thyroid gland by interfering with iodine uptake, which can, as a result, cause an enlargement of the thyroid (a goitre or goiter)
What are some other thyroid-suppressing foods?
Pine nuts
Peanuts
Millet
Strawberries
Pears
Peaches
Spinach
Bamboo shoots
Radishes
Horseradish
Sweet Potatoes
Vegetables in the genus Brassica:
Bok choy
Broccoli
Broccolini (Asparations)
Brussels sprouts
Cabbage
Canola
Cauliflower
Chinese cabbage
Choy sum
Collard greens
Kai-lan (Chinese broccoli)
Kale
Kohlrabi
Mizuna
Mustard greens
Rapeseed (yu choy)
Rapini
Rutabagas
Tatsoi
Turnips
What are some drugs that are also goitrogens?
--thoiureas (thoiuracil, propylthiouracil)
--mercaptoimidazole
--lithium interferes with hormone release
--cobalt
--high dose iodide
--sulfadimethoxine, propylthiouracil, potassium perchlorate, and iopanoic acids
--some oxazolidines such as goitrin
--thiocyanate overload (cassava as food source, Central Africa), esp if selenium def
(Ions such as thiocyanate and perchlorate decrease iodide uptake by competitive inhibition)
--amiodarone inhibits peripheral conversion of T4 to T3 & interferes with hormone action
--phenobarbitone, phenytoin, carbamazepine, rifampin induce degradation of T3 and T4
What's another word for goiter?
struma
What do you call a goiter teratoma on the ovary?
Struma ovarii
What is jod-basedow disease?
Hyperthyroid due to iodine overdose
What is thyrotoxicosis?
The overflow release of stored preformed T3 and T4 due to infection, lasting 2-3 weeks.
Who presents with apathetic hyperthyroidism?
Elders, age 70+ who may present with sx of hypothyroid or exacerbated CHF
What is the broad differential for hyperthyroidism?
Graves disease, thyrotroph adenoma, thryoiditis, struma ovarii, iodine excess, factitious, toxic multinodular goiter, neonatal thyrotoxicosis
What are some of the signs and symptoms of hyperthyroidism?
Nervousness, find hand tremor, emotional lability, fatigue, muscle weakness
weight loss dt anorexia
heat intolerance
warm moist skin, flushing, perspiring
persistent generalized LAD
SOB
goiter
Heart palpitations, tachyarrhythmias, rapid pulse, cardiomegaly/myopathy
pretibial myxedema (doesn't pit)
diarrhea or frequent stools, decreased transit time
breast enlargement (men too), amenorrhea, oligomenorrhea
opthalmopathies: lid retraction, lid lag (hesitation before closing), proptosis = exopthalamos
osteoporosis
muscle atrophy
fatty liver
Why is there breast enlargement in hypothyroid males? ???
Incr TSH-->liver-->more sex hormone binding globulin-->binds T-->relatively more estrogen
What is the etiology of exopthalamos in hyperthyroid?
Deposition of glycosaminoglycans behind the eye
What do you call hypothyroidism in neonates?
Cretinism
What other condition looks like cretinism and may occur in association with it?
Down's syndrome
How is cretinism prevented in developed nations?
Early detection of hypothyroid by heel stick at birth
What are the main etiologies of hypothyroidism?
Atrophic autoimmune, Hashimotos, or thyroid resection or destruction by radiation, drugs
pituitary or hypothalamic dz, iodine deficiency, goitrogens, dequervain thyroidisit, Down syndrome
What happened at Hanford?
The government released radioactive iodine into the western flow of the Columbia river
in the 1950-60's
as an experiment, exposed in the 1990's
“the green run”, “downwinders”
many cases of thyroid disease occurred due to this experiment
What is an achiliometer?
An old device used by early naturopaths to measure achilles DTR; a slow return=>hypo.
What are some of the signs and symptoms of hypothyroidism?
Slow mentation, fatigue, lethargy, apathy
low basal temperature, cold intolerance, decreased sweating
delayed DTRs or return
constipation
heart enlarged, dilated, cardiomyopathy
dry, coarse skin and hair
diffuse hair loss, loss of lateral 1/3 of eyebrow, loss of pubic & axillary hair
thick tongue, lumpy with teeth imprints
periorbital edema, voice changes, coarse features
loss of visual and auditory acuity
psychosis = “myxedema madness”, only in severe cases
menstrual changes
proximal weakness
What is Wilson disease?
Too much copper
What is Wilson syndrome?
Hypothyroidism with normal TSH levels
(due to overproduction of inactive rT3)
What is Wilson's preferred treatment for hypothyroidism?
Time release T3 capsules, if pulse goes over 100 call.
How do you diagnose hypothyroidism?
Elevated TSH
What is the more common name for struma lymphomatosa or lymphadenoid goiter?
Hashimoto thyroiditis
What is the most common cause of goitrous hypothyroism in non-goiter areas?
Hashimotos
Which HLA's are associated with Hashimotos?
HLA DR3 and DR5
What are the autoantibodies produced in Hashimotos?
Anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TGB)
Which immune cells are defective to allow the production of autoantibodies?
CD4+ suppressor T cells
If the thyroid destruction is not due to antibodies, what else could cause it?
Cell mediated destruction (CD8 killer T cells) or due to RAI exposure
What is RAI?
radioactive iodine
What cytokine is produced that causes destruction of thyroid tissue?
Interferon gamma
What are some other conditions that may occur in the same patient as one with Hashimotos?
SLE, sjogren, RA, celiac, AI liver dz, PA, DM 1, Grave, vitiligo, Addison, B-cell Hodgkin lymphoma
Which of the previous list is not autoimmune but shows 200x more risk with Hashimotos?
Hodgkin lymphoma
If a patient has elevated transaminases, what else would you consider besides autoimmune liver dz?
Hepatitis dt alcoholism, viral, NASH
Name the cells from degenerated follicle epithelia that may be present in Hashimotos?
HURTHLE cells (oncocytes)
What do hurthle cells look like?
Like Mallory bodies, they are eosinophilic and hyaline in appearance
Will a patient with Hashimotos present as hyper, hypo, or euthyroid?
All of the above. Most are euthyroid. Some have a transient hyperthyroid period and many experience hypothyroidism.
What's the name for the transient hyperthyroid period?
thyroiditis, or more humorously:
Hashitoxicosis, or Toximoto's Dz
What is Reidel thyroiditis?
A rare condition in old women in which the thyroid is larger and harder than with Hashimotos
rock-hard, woody feeling
desmoplasia beyond the gland ???
may cause hypothyroidism or dyspnea
What is another name for subacute granulomatous thyroiditis?
Dequervain or giant cell thyroiditis
What causes a persistent sore throat with a painful thyroid and fever?
Dequervain or giant cell thyroiditis, aka subacute granulomatous thyroiditis
Which HLA is usually present in subacute granulomatous thyroiditis?
HLA-B35
What viral diseases may also trigger it?
Coxackievirus, echovirus, mumps, measles, flu, adenovirus
What are the signs of subacute granulomatous thyroiditis?
besides sore throat, painful thyroid and fever?
Early hyper, late hypo, recovery euthyroid
high sed rate
sudden enlargement of thyroid (pain)
Who gets Grave's disease?
Women, 7:1
What is the antibody attacking in Grave's?
It's an IgG response to the TSH receptor-->long acting thyroid stimulator
aka TSI = thyroid stimulating immunoglobulin
Intrathyroidal CD4+ cells sensitized to TSH receptor secrete IFN gamma and TNF
-->expression of HLA and costimulatory molecules on thyroid epithelia
-->presentation of thyroid antigen
How hereditary is Grave's?
There is 50% concordance in identical twins
related with HLA-B8, DR3
Does GWBush have it??? why did I make that note???
What is the morphology of thyroid follicles in Grave's disease?
Follicles are scalloped in appearance, “all chewed up”
Excess tall columnar lining cells erode colloid and cause SCALLOPED appearance of follicles
extrathyroidal tissue such as the orbit MAY be affected dt fibroblasts expressing TSH receptors and secreting GAGs
What are some of the signs and symptoms of Grave's disease?
proptosis/exopthalamos-->dry eyes, corneal ulcers
jitters, weight loss
increased heartbeat, muscle weakness, disturbed sleep, and irritability
What lab values do you expect for Grave's?
low TSH, high T3 and 4
TSI, anti-TGB, anti-TPO (same as Hashimotos)
What is TSI?
Thyroid stimulating immunoglobulin
see text p1172
What is TSI most specific for?
Graves
What foods stimulate thyroid function?
avocado, coconut
What do rats get when you give them excess caffeine in conjunction with a lack of iodine?
thyroid cancers
Son HY, Nishikawa A, Kanki K, et al. (2003). "Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine". Cancer Sci. 94 (4): 334-7. doi:10.1111/j.1349-7006.2003.tb01442.x. PMID 12824900.
What are some etiologies of simple goiters, aka diffuse non-toxic or simple colloid goiters?
deficient iodine
goitrogens: brassica, cabbage, cassava
hard water: calcium and fluoride in water
plastics: estrogens or RAI in water
RAI = ???
Who gets simple goiters the most?
females after puberty
often in pregnancy
often hereditary influence
most are euthyroid
What sequela might come from an untreated simple goiter?
multinodular goiter
What are two treatments for simple goiter?
iodine if used early
best: thyroxine to take a load off the anterior pituitary and prevent multinodular goiter
What enzyme links iodine to tyrosine?
peroxidase
What hereditary tendencies could induce goiters?
poor GI absorption of iodine
lack of peroxidase (links iodine to tyrosine)
can't recycle iodine in thyroid
can't link two iodotyrosine moieties to make T4
Multinodular goiters may be non-toxic or ?
thyrotoxic
Name the disease associated with thyrotoxic multinodular goiters.
Plummer dz
Which goiters are the largest, and can "plunge" behind the sternum?
thyrotoxic multinodular, aka Plummer dz
What sx might be caused by a large multinodular goiter?
dysphagia
disfigurement
choking sensation
inspiratory stridor
Which goiters are most often mistaken for cancer?
thyrotoxic multinodular, aka Plummer dz
What do you find with a biopsy of a multinodular goiter?
scarring, hemorrhage, calcification, cysts filled with air or brown fluid
colloid-filled follicles with hypertrophy and hyperplasia of epithelium
What sort of cyst might be found midline just below the angle of the jaw?
thyroglossal duct cyst
What's the etiology of a thyroglossal duct cyst?
congenital
What's inside such a cyst?
mucin
What could such a cyst become?
an abscess or malignancy
Which is more likely to become cancer, solitary or multiple nodules?
solitary
What percentage of people have solitary thyroid nodes?
2-4%
How big are they usually?
3-10cm
Are you worried if a young person has nodules?
yes, more likely neoplasm
Are you concerned if the nodule is "hot"?
not so much, more likely to be benign
Nodules in which gender are more likely to be neoplastic?
males
What's the differential for a solitary node?
cyst, adenoma, carcinoma, dominant nodule in multinodular or Hashimoto goiter
How do you diagnose thyroid nodules?
iodine uptake scan, PE, fine needle aspiration
What is a risk factor for malignant thyroid neoplasms?
irradiation of head and neck esp younger than 20
What percentage of solitary thyroid nodules are adenomas?
99% (not neoplastic)
What might you find in the center of an adenoma?
fibrosis or hemorrhage
Are they usually hot, warm, or cold?
cold
What's the major differential for a cold adenoma?
carcinoma
What's the most common kind of thyroid carcinoma?
papillary carcinoma (75-80%)
What hormone do they have receptors for?
estrogen
What is the usual cell of origin for thyroid neoplasms?
follicular epithelium
What do follicular epithelial cells make?
calcitonin
Who gets papillary carcinomas?
3:1 female
age 20-50
What's the histopathology of papillary?
"Orphan Annie eye" look, nuclei are pale dt diffuse chromatin
aka ground glass appearance
What's more specific for papillary than empty nuclei?
intranuclear inclusions: psammomma bodies = lamellar calcifications
Where else do you see psammomma bodies?
prostate cancer
What's the prognosis if you see psammomma bodies?
good even tho they're usu cold and often spread to LN's
ten year survival for all thyroid papillary is over 95%
If thyroid papillary carcinoma metastasizes, where do the mets go?
LUNGS mainly
also bone, brain (rare)
Papillary carcinoma is usually asymptomatic, but if you have sx, what will they be?
hoarseness, dysphagia, cough, dyspnea
there are usually cervical mets present at Dx
If you find mets in the thyroid, where did they probably originate?
breast, kidney, lung, CRC
What's the second most common primary thyroid cancer?
follicular carcinoma (10-20% of thyroid CA)
10 year survival for larger tumors is 50%
most are cold, may be warm
What percentage of follicular has the RAS mutation?
50%
Where does follicular like to metastasize to?
bone, lung, liver (hematogenous spread)
Which cell in the thyroid makes calcitonin?
the C cell
What is the effect of calcitonin?
lowers serum calcium
What else do C cells make?
VIP, serotonin, somatostatin, ACTH
What cancer originates in C cells?
medullary
Describe medullary carcinomas.
may be solitary or multiple nodules
has polygonal or spindle-shaped cells
often contains amyloid in the stroma (amyloid from altered calcitonin)
What's the rare but deadly form of thyroid cancer?
anaplastic, 5% of all thyroid CA, almost 100% mortality rate
age 65 +
50% have hx of multinodular goiter
many have hx of more differentiated thyroid CA
p53 lost
Name three bone tropic hormones.
tryrocalcitonin
estrogen (esp E1 and E2)
progesterone
testosterone
DHEA
Name two bone resorptive hormones.
PTH, T3, T4, cortisol
Dequervain or giant cell thyroiditis, aka subacute granulomatous thyroiditis
more in women 10-40???
An elder whose CHF has just gotten worse may have what thyroid condition?
"apathetic" hypothyroidism
If someone just had a coxsackie virus infection and now is hyperthyroid, what do you suspect?
subacute granulomatous thyroiditis
What is the morphology of thyroid follicles in Grave's disease?
Follicles are scalloped in appearance, “all chewed up”
What is TSI most specific for?
Graves
What two diseases have both anti-thyroglobulin and anti-thyroperoxidase antibodies?
Hashimotos and Graves
What enzyme links iodine to tyrosine?
peroxidase
Which goiters are the largest, and can "plunge" behind the sternum?
thyrotoxic multinodular, aka Plummer dz, most mistaken for cancer
What kind of thyroiditis makes the gland wooden or rock-hard?
Reidel thyroiditis, rare condition in older women, may cause hypothyroidism or dyspnea
What percentage of solitary thyroid nodules are adenomas?
99%
What kind of thyroid carcinoma shows "Orphan Annie eye" nuclei?
papillary
also as psammomma bodies
What's the most common kind of thyroid carcinoma?
papillary carcinoma (75-80%)
What hormone do they have receptors for?
estrogen
What is the usual cell of origin for thyroid neoplasms?
follicular epithelium
What less common cancer arises from C cells in the follicular epithelium?
medullary carcinoma
What do C cells make?
calcitonin
VIP, serotonin, somatostatin, ACTH
(calcitonin used as tumor marker for medullary)
What's the second most common primary thyroid cancer?
follicular carcinoma (10-20% of thyroid CA)
10 year survival for larger tumors is 50%
most are cold, may be warm
Name three bone tropic hormones.
thryrocalcitonin
estrogen (esp E1 and E2)
progesterone
testosterone
DHEA
Name two bone resorptive hormones.
PTH, T3, T4, cortisol
How may raw cruciferous vegetables and African cassava (aka tapioca) affect the thyroid?
They are goitrogens, ie. they suppress the function of the thyroid gland by interfering with iodine uptake, which can, as a result, cause an enlargement of the thyroid (a goitre or goiter)
What are some other thyroid-suppressing foods?
Pine nuts
Peanuts
Millet
Strawberries
Pears
Peaches
Spinach
Bamboo shoots
Radishes
Horseradish
Sweet Potatoes
Vegetables in the genus Brassica:
Bok choy
Broccoli
Broccolini (Asparations)
Brussels sprouts
Cabbage
Canola
Cauliflower
Chinese cabbage
Choy sum
Collard greens
Kai-lan (Chinese broccoli)
Kale
Kohlrabi
Mizuna
Mustard greens
Rapeseed (yu choy)
Rapini
Rutabagas
Tatsoi
Turnips
What are some drugs that are also goitrogens?
--thoiureas (thoiuracil, propylthiouracil)
--mercaptoimidazole
--lithium interferes with hormone release
--cobalt
--high dose iodide
--sulfadimethoxine, propylthiouracil, potassium perchlorate, and iopanoic acids
--some oxazolidines such as goitrin
--thiocyanate overload (cassava as food source, Central Africa), esp if selenium def
(Ions such as thiocyanate and perchlorate decrease iodide uptake by competitive inhibition)
--amiodarone inhibits peripheral conversion of T4 to T3 & interferes with hormone action
--phenobarbitone, phenytoin, carbamazepine, rifampin induce degradation of T3 and T4
What's another word for goiter?
struma
What do you call a goiter teratoma on the ovary?
Struma ovarii
What is jod-basedow disease?
Hyperthyroid due to iodine overdose
What is thyrotoxicosis?
The overflow release of stored preformed T3 and T4 due to infection, lasting 2-3 weeks.
Who presents with apathetic hyperthyroidism?
Elders, age 70+ who may present with sx of hypothyroid or exacerbated CHF
What is the broad differential for hyperthyroidism?
Graves disease, thyrotroph adenoma, thryoiditis, struma ovarii, iodine excess, factitious, toxic multinodular goiter, neonatal thyrotoxicosis
What are some of the signs and symptoms of hyperthyroidism?
Nervousness, find hand tremor, emotional lability, fatigue, muscle weakness
weight loss dt anorexia
heat intolerance
warm moist skin, flushing, perspiring
persistent generalized LAD
SOB
goiter
Heart palpitations, tachyarrhythmias, rapid pulse, cardiomegaly/myopathy
pretibial myxedema (doesn't pit)
diarrhea or frequent stools, decreased transit time
breast enlargement (men too), amenorrhea, oligomenorrhea
opthalmopathies: lid retraction, lid lag (hesitation before closing), proptosis = exopthalamos
osteoporosis
muscle atrophy
fatty liver
Why is there breast enlargement in hypothyroid males? ???
Incr TSH-->liver-->more sex hormone binding globulin-->binds T-->relatively more estrogen
What is the etiology of exopthalamos in hyperthyroid?
Deposition of glycosaminoglycans behind the eye
What do you call hypothyroidism in neonates?
Cretinism
What other condition looks like cretinism and may occur in association with it?
Down's syndrome
How is cretinism prevented in developed nations?
Early detection of hypothyroid by heel stick at birth
What are the main etiologies of hypothyroidism?
Atrophic autoimmune, Hashimotos, or thyroid resection or destruction by radiation, drugs
pituitary or hypothalamic dz, iodine deficiency, goitrogens, dequervain thyroidisit, Down syndrome
What happened at Hanford?
The government released radioactive iodine into the western flow of the Columbia river
in the 1950-60's
as an experiment, exposed in the 1990's
“the green run”, “downwinders”
many cases of thyroid disease occurred due to this experiment
What is an achiliometer?
An old device used by early naturopaths to measure achilles DTR; a slow return=>hypo.
What are some of the signs and symptoms of hypothyroidism?
Slow mentation, fatigue, lethargy, apathy
low basal temperature, cold intolerance, decreased sweating
delayed DTRs or return
constipation
heart enlarged, dilated, cardiomyopathy
dry, coarse skin and hair
diffuse hair loss, loss of lateral 1/3 of eyebrow, loss of pubic & axillary hair
thick tongue, lumpy with teeth imprints
periorbital edema, voice changes, coarse features
loss of visual and auditory acuity
psychosis = “myxedema madness”, only in severe cases
menstrual changes
proximal weakness
What is Wilson disease?
Too much copper
What is Wilson syndrome?
Hypothyroidism with normal TSH levels
(due to overproduction of inactive rT3)
What is Wilson's preferred treatment for hypothyroidism?
Time release T3 capsules, if pulse goes over 100 call.
How do you diagnose hypothyroidism?
Elevated TSH
What is the more common name for struma lymphomatosa or lymphadenoid goiter?
Hashimoto thyroiditis
What is the most common cause of goitrous hypothyroism in non-goiter areas?
Hashimotos
Which HLA's are associated with Hashimotos?
HLA DR3 and DR5
What are the autoantibodies produced in Hashimotos?
Anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TGB)
Which immune cells are defective to allow the production of autoantibodies?
CD4+ suppressor T cells
If the thyroid destruction is not due to antibodies, what else could cause it?
Cell mediated destruction (CD8 killer T cells) or due to RAI exposure
What is RAI?
radioactive iodine
What cytokine is produced that causes destruction of thyroid tissue?
Interferon gamma
What are some other conditions that may occur in the same patient as one with Hashimotos?
SLE, sjogren, RA, celiac, AI liver dz, PA, DM 1, Grave, vitiligo, Addison, B-cell Hodgkin lymphoma
Which of the previous list is not autoimmune but shows 200x more risk with Hashimotos?
Hodgkin lymphoma
If a patient has elevated transaminases, what else would you consider besides autoimmune liver dz?
Hepatitis dt alcoholism, viral, NASH
Name the cells from degenerated follicle epithelia that may be present in Hashimotos?
HURTHLE cells (oncocytes)
What do hurthle cells look like?
Like Mallory bodies, they are eosinophilic and hyaline in appearance
Will a patient with Hashimotos present as hyper, hypo, or euthyroid?
All of the above. Most are euthyroid. Some have a transient hyperthyroid period and many experience hypothyroidism.
What's the name for the transient hyperthyroid period?
thyroiditis, or more humorously:
Hashitoxicosis, or Toximoto's Dz
What is Reidel thyroiditis?
A rare condition in old women in which the thyroid is larger and harder than with Hashimotos
rock-hard, woody feeling
desmoplasia beyond the gland ???
may cause hypothyroidism or dyspnea
What is another name for subacute granulomatous thyroiditis?
Dequervain or giant cell thyroiditis
What causes a persistent sore throat with a painful thyroid and fever?
Dequervain or giant cell thyroiditis, aka subacute granulomatous thyroiditis
Which HLA is usually present in subacute granulomatous thyroiditis?
HLA-B35
What viral diseases may also trigger it?
Coxackievirus, echovirus, mumps, measles, flu, adenovirus
What are the signs of subacute granulomatous thyroiditis?
besides sore throat, painful thyroid and fever?
Early hyper, late hypo, recovery euthyroid
high sed rate
sudden enlargement of thyroid (pain)
Who gets Grave's disease?
Women, 7:1
What is the antibody attacking in Grave's?
It's an IgG response to the TSH receptor-->long acting thyroid stimulator
aka TSI = thyroid stimulating immunoglobulin
Intrathyroidal CD4+ cells sensitized to TSH receptor secrete IFN gamma and TNF
-->expression of HLA and costimulatory molecules on thyroid epithelia
-->presentation of thyroid antigen
How hereditary is Grave's?
There is 50% concordance in identical twins
related with HLA-B8, DR3
Does GWBush have it??? why did I make that note???
What is the morphology of thyroid follicles in Grave's disease?
Follicles are scalloped in appearance, “all chewed up”
Excess tall columnar lining cells erode colloid and cause SCALLOPED appearance of follicles
extrathyroidal tissue such as the orbit MAY be affected dt fibroblasts expressing TSH receptors and secreting GAGs
What are some of the signs and symptoms of Grave's disease?
proptosis/exopthalamos-->dry eyes, corneal ulcers
jitters, weight loss
increased heartbeat, muscle weakness, disturbed sleep, and irritability
What lab values do you expect for Grave's?
low TSH, high T3 and 4
TSI, anti-TGB, anti-TPO (same as Hashimotos)
What is TSI?
Thyroid stimulating immunoglobulin
see text p1172
What is TSI most specific for?
Graves
What foods stimulate thyroid function?
avocado, coconut
What do rats get when you give them excess caffeine in conjunction with a lack of iodine?
thyroid cancers
Son HY, Nishikawa A, Kanki K, et al. (2003). "Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine". Cancer Sci. 94 (4): 334-7. doi:10.1111/j.1349-7006.2003.tb01442.x. PMID 12824900.
What are some etiologies of simple goiters, aka diffuse non-toxic or simple colloid goiters?
deficient iodine
goitrogens: brassica, cabbage, cassava
hard water: calcium and fluoride in water
plastics: estrogens or RAI in water
RAI = ???
Who gets simple goiters the most?
females after puberty
often in pregnancy
often hereditary influence
most are euthyroid
What sequela might come from an untreated simple goiter?
multinodular goiter
What are two treatments for simple goiter?
iodine if used early
best: thyroxine to take a load off the anterior pituitary and prevent multinodular goiter
What enzyme links iodine to tyrosine?
peroxidase
What hereditary tendencies could induce goiters?
poor GI absorption of iodine
lack of peroxidase (links iodine to tyrosine)
can't recycle iodine in thyroid
can't link two iodotyrosine moieties to make T4
Multinodular goiters may be non-toxic or ?
thyrotoxic
Name the disease associated with thyrotoxic multinodular goiters.
Plummer dz
Which goiters are the largest, and can "plunge" behind the sternum?
thyrotoxic multinodular, aka Plummer dz
What sx might be caused by a large multinodular goiter?
dysphagia
disfigurement
choking sensation
inspiratory stridor
Which goiters are most often mistaken for cancer?
thyrotoxic multinodular, aka Plummer dz
What do you find with a biopsy of a multinodular goiter?
scarring, hemorrhage, calcification, cysts filled with air or brown fluid
colloid-filled follicles with hypertrophy and hyperplasia of epithelium
What sort of cyst might be found midline just below the angle of the jaw?
thyroglossal duct cyst
What's the etiology of a thyroglossal duct cyst?
congenital
What's inside such a cyst?
mucin
What could such a cyst become?
an abscess or malignancy
Which is more likely to become cancer, solitary or multiple nodules?
solitary
What percentage of people have solitary thyroid nodes?
2-4%
How big are they usually?
3-10cm
Are you worried if a young person has nodules?
yes, more likely neoplasm
Are you concerned if the nodule is "hot"?
not so much, more likely to be benign
Nodules in which gender are more likely to be neoplastic?
males
What's the differential for a solitary node?
cyst, adenoma, carcinoma, dominant nodule in multinodular or Hashimoto goiter
How do you diagnose thyroid nodules?
iodine uptake scan, PE, fine needle aspiration
What is a risk factor for malignant thyroid neoplasms?
irradiation of head and neck esp younger than 20
What percentage of solitary thyroid nodules are adenomas?
99% (not neoplastic)
What might you find in the center of an adenoma?
fibrosis or hemorrhage
Are they usually hot, warm, or cold?
cold
What's the major differential for a cold adenoma?
carcinoma
What's the most common kind of thyroid carcinoma?
papillary carcinoma (75-80%)
What hormone do they have receptors for?
estrogen
What is the usual cell of origin for thyroid neoplasms?
follicular epithelium
What do follicular epithelial cells make?
calcitonin
Who gets papillary carcinomas?
3:1 female
age 20-50
What's the histopathology of papillary?
"Orphan Annie eye" look, nuclei are pale dt diffuse chromatin
aka ground glass appearance
What's more specific for papillary than empty nuclei?
intranuclear inclusions: psammomma bodies = lamellar calcifications
Where else do you see psammomma bodies?
prostate cancer
What's the prognosis if you see psammomma bodies?
good even tho they're usu cold and often spread to LN's
ten year survival for all thyroid papillary is over 95%
If thyroid papillary carcinoma metastasizes, where do the mets go?
LUNGS mainly
also bone, brain (rare)
Papillary carcinoma is usually asymptomatic, but if you have sx, what will they be?
hoarseness, dysphagia, cough, dyspnea
there are usually cervical mets present at Dx
If you find mets in the thyroid, where did they probably originate?
breast, kidney, lung, CRC
What's the second most common primary thyroid cancer?
follicular carcinoma (10-20% of thyroid CA)
10 year survival for larger tumors is 50%
most are cold, may be warm
What percentage of follicular has the RAS mutation?
50%
Where does follicular like to metastasize to?
bone, lung, liver (hematogenous spread)
Which cell in the thyroid makes calcitonin?
the C cell
What is the effect of calcitonin?
lowers serum calcium
What else do C cells make?
VIP, serotonin, somatostatin, ACTH
What cancer originates in C cells?
medullary
Describe medullary carcinomas.
may be solitary or multiple nodules
has polygonal or spindle-shaped cells
often contains amyloid in the stroma (amyloid from altered calcitonin)
What's the rare but deadly form of thyroid cancer?
anaplastic, 5% of all thyroid CA, almost 100% mortality rate
age 65 +
50% have hx of multinodular goiter
many have hx of more differentiated thyroid CA
p53 lost
Name three bone tropic hormones.
tryrocalcitonin
estrogen (esp E1 and E2)
progesterone
testosterone
DHEA
Name two bone resorptive hormones.
PTH, T3, T4, cortisol